The aim of the proposed research is to determine the instance and rate of development of degenerative complications of diabetes mellitus in relation to treatment. Patients with diabetes mellitus selected according to specific criteria have been placed by random selection into one of four treatment groups. The groups include: diet plus oral placebo, diet plus tolbutamide, diet plus insulin related to body surface area and diet plus insulin to control blood glucose (below 150 milligrams per cent) in the post prandial period. Observations are being made for evidence of degenerative complications of the cardio-vascular peripheral vascular, renal, neurological and ophthalmologic systems. To insure uniformity of methodology and to include in the study a large number of diabetic patients under various social, geographical and racial circumstances, the study is being made by twelve university centers. A central co-ordinating unit is being used to provide the necessary epidemiologic guidance and analysis of the study results.